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Description of key information

Acute Oral

Sax's Handbook

According to the handbook data the acute oral LD50 to rats is 5000 mg/kg, the acute oral LD50 to mice is 3460 mg/kg and the lethal dose low to the rabbit is 2550 mg/kg.

Food and Chemical Toxicology

The acute oral LD50 of the substance to rabbits was reported to be 2.5 - 3.2 g/kg with production of ataxia, gasping respirations and hypothermia at lethal dose levels (Browning, 1965, and Fasset, 1963) and 2.02 g/kg by Munch (1972).

Acute Inhalation

SafePharm Laboratories - EU Method B.4 (rat)

Only one death occurred in a group of ten rats exposed to a mean achieved atmosphere concentration of 22.7 mg/L for four hours. It was therefore considered that the acute inhalation median lethal concentration (4 hr LC50) of the test material, in the Sprague-Dawley rat, was greater than 22.7 mg/L.

Sax's Handbook

According to handbook data the acute inhalation LC50 of the substance to mice is 27 g/m³.

Acute Dermal Toxicity

Food and Chemical Toxicology

According to information in secondary literature, the acute dermal LD50 of the substance to the rabbit is in excess of 5000 mg/kg.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
Valid with restrictions. This is peer reviewed data where the test methodology and identity of the substance have been evaluated, and a reliable and representative value for the endpoint has been selected. No information on GLP status or test guideline followed is available.
Reference:
Composition 0
Qualifier:
no guideline followed
Principles of method if other than guideline:
Handbook data does not specify the method. Data from peer reviewed source.
GLP compliance:
not specified
Test type:
other: Handbook data does not specify the method. Data from peer reviewed source.
Test material information:
Composition 1
Species:
other: rat, mouse and rabbit
Strain:
not specified
Route of administration:
oral: unspecified
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
5 000 mg/kg bw
Based on:
not specified
Remarks on result:
other: rat
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
3 460 mg/kg bw
Based on:
not specified
Remarks on result:
other: mouse
Key result
Sex:
not specified
Dose descriptor:
LDLo
Effect level:
2 550 mg/kg bw
Based on:
not specified
Remarks on result:
other: rabbit
Interpretation of results:
study cannot be used for classification
Conclusions:
According to the handbook data the acute oral LD50 to rats is 5000 mg/kg, the acute oral LD50 to mice is 3460 mg/kg and the lethal dose low to the rabbit is 2550 mg/kg.
Executive summary:

According to the handbook data the acute oral LD50 to rats is 5000 mg/kg, the acute oral LD50 to mice is 3460 mg/kg and the lethal dose low to the rabbit is 2550 mg/kg.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
not specified
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Reference:
Composition 0
Qualifier:
no guideline followed
Principles of method if other than guideline:
No information on test method provided. The results presented in this publication make reference to:
Browning, 1965 (Browning, E. (1965). Toxicity and Metabolism of Industrial Solvents. p 574. Elsevier Publishing Co., London)
Fassett, 1963 (Fassett, D. (1963) Esters. In Industrial Hygiene and Toxicology. 2nd Ed. Edited by F.A. Patty. Vol. II p. 1865. Interscience Publishers, New York)
Munch, 1972 (Munch, J.C. (1972). Aliphatic alcohols and alkyl esterst. Narcotic and lethal potencies to tadpoles and to rabbits. Ind. Med. Surg. 41 (4). 31)
GLP compliance:
not specified
Test material information:
Composition 1
Species:
rabbit
Route of administration:
oral: unspecified
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
2 500 - 3 200 mg/kg bw
Based on:
test mat.
Remarks on result:
other: reference: Browning, 1965 & Fassett, 1963
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
2 002 mg/kg bw
Based on:
test mat.
Remarks on result:
other: reference: Munch, 1972
Other findings:
Production of ataxia, gasping respirations and hypothermian seen by Browning (1965) an Fassett (1963)
Interpretation of results:
study cannot be used for classification
Conclusions:
The acute oral LD50 of the substance to rabbits was reported to be 2.5 - 3.2 g/kg with production of ataxia, gasping respirations and hypothermia at lethal dose levels (Browning, 1965, and Fasset, 1963) and 2.02 g/kg by Munch (1972).
Executive summary:

The acute oral LD50 of the substance to rabbits was reported to be 2.5 - 3.2 g/kg with production of ataxia, gasping respirations and hypothermia at lethal dose levels (Browning, 1965, and Fasset, 1963) and 2.02 g/kg by Munch (1972).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
Valid with restrictions. This is peer reviewed data where the test methodology and identity of the substance have been evaluated, and a reliable and representative value for the endpoint has been selected. No information on GLP status or test guideline followed is available.
Reference:
Composition 0
Qualifier:
no guideline followed
Principles of method if other than guideline:
Handbook data does not specify the method. Data from peer reviewed source.
GLP compliance:
not specified
Test type:
other: Handbook data does not specify the method. Data from peer reviewed source.
Species:
mouse
Strain:
not specified
Sex:
not specified
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Key result
Sex:
not specified
Dose descriptor:
LC50
Effect level:
27 other: g/m³
Based on:
not specified
Remarks on result:
other: exposure duration not specified
Interpretation of results:
study cannot be used for classification
Conclusions:
According to handbook data the acute inhalation LC50 of the substance to mice is 27 g/m³.
Executive summary:

According to handbook data the acute inhalation LC50 of the substance to mice is 27 g/m³.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
13 November 2003 to 02 January 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reference:
Composition 0
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
traditional method
Limit test:
yes
Test material information:
Composition 1
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation:
8 - 12 weeks old
- Weight at study initiation:
200 - 350 g
- Housing:
animals were housed in groups of 5 by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes
- Diet: ad libitum (except during exposure period)
- Water: ad libitum (except during exposure period)
- Acclimation period:
at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
21 ± 2°C
- Humidity (%):
55 ± 15
- Air changes (per hr):
at least 15 air changes per hour
- Photoperiod (hrs dark / hrs light):
12 hours dark / 12 hours light
Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
The test material was vaporised by injecting it directly into the air supply to the exposure chamber. The material was contained in a glass syringe located on an infusion pump thus providing a constant supply of test material into the air stream. Immediately after the injection site, the air supply was ducted, via suitable tubing and two conical flasks in series, through a water bath, maintained at approximately 70°C, to ensure complete vaporisation.
Compressed air was supplied by means of an oil free compressor and passed through a water trap and respiratory quality filters before it was introduced to the test material.
The cylindrical exposure chamber had a volume of approximately 30 litres (dimensions: 28 cm diameter x 50 cm high). The concentration within the exposure chamber was controlled by adjusting the rate of the infusion pump. The extract from the exposure chamber passed through a ‘scrubber’ trap and was connected with a high efficiency filter to a metered exhaust system. The chamber was maintained under negative pressure. A schematic diagram of the dynamic (continuous flow) system employed is shown in Figure 1 (attached).
Prior to the start of the study, test material atmospheres were generated within the exposure chamber. During this characterisation period air flow settings and test material input rates were varied to achieve the required atmospheric concentrations.

EXPOSURE PROCEDURE
Each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber ‘O’ ring. Only the nose of each animal was exposed to the test atmosphere.
Following an appropriate equilibration period a single group of ten rats (five males and five females) was exposed to an atmosphere of the test material for a period of four hours. A target concentration of 20 mg/L was used for the exposure. As only one death occurred and the mean achieved concentration was 114% of target, no further levels were required.

EXPOSURE CHAMBER TEMPERATURE AND RELATIVE HUMIDITY
The temperature and relative humidity inside the exposure chamber were measured by an electronic thermometer/humidity meter located in a vacant port in the animals’ breathing zone of the chamber and recorded every thirty minutes throughout the four-hour exposure period.

EXPOSURE CHAMBER OXYGEN CONCENTRATION
Oxygen levels within the exposure chamber were measured by an electronic oxygen analyser located in a sampling port in the animals breathing zone during each exposure period. The test atmosphere was generated to contain at least 19% oxygen.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
22.7 mg/L (mean achieved)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were observed for clinical signs at hourly intervals during exposure, immediately on removal from the restraining tubes at the end of exposure, one hour after termination of exposure and subsequently once daily for fourteen days. Any deaths or evidence of overt toxicity were recorded at each observation.
- Individual bodyweights were recorded prior to treatment on the day of exposure and on Days 7 and 14 or at death.
- Necropsy of survivors performed: yes (at the end of the fourteen day observation period the surviving animals were killed by intravenous overdose of sodium pentobarbitone. All animals, including those that died during the study, were subjected to a full external and internal examination, and any macroscopic abnormalities were recorded. The respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity.)
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 22.7 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
One male animal died after 67 minutes exposure. This death is difficult to explain given the lack of clinical signs exhibited by any of the other animals during or after exposure.
Clinical signs:
Signs of hunched posture, pilo-erection and red/brown staining around the eyes are commonly seen in animals for short periods on removal from the chamber following 4-hour inhalation studies. Wet fur is commonly recorded both during and for a short period after exposure. These observations are considered to be associated with the restraint procedure and, in isolation, are not indicative of toxicity.
In addition to the observations considered to be due to the restraint procedure and an isolated instance of laboured respiration after 60 minutes exposure, clinical signs were limited to increased respiratory rate only. This was observed in all animals during exposure and on removal from the chamber. One hour after exposure, no significant clinical signs were noted amongst the group and the animals appeared normal throughout the observation period.
Body weight:
Normal bodyweight development was noted during the study.
Gross pathology:
No macroscopic abnormalities were detected amongst animals necropsied at terminal kill. The animal that died during the study showed abnormally red lungs.
Other findings:
Exposure Chamber Concentration
The actual concentration of the test material was measured off-line by gas chromatography (GC). The test atmospheres were sampled after theoretical chamber equilibration and then at approximately hourly intervals during the exposure period. The mean values obtained were:
- Mean Achieved: 22.7 mg/L
- Standard deviation: 1.56
- Nominal: 19.1 mg/L

The chamber flow rate was maintained at 20 L/min providing 40 air changes per hour.
Interpretation of results:
other: Not classified in accordance with EU criteria
Conclusions:
Only one death occurred in a group of ten rats exposed to a mean achieved atmosphere concentration of 22.7 mg/L for four hours. It was therefore considered that the acute inhalation median lethal concentration (4 hr LC50) of the test material, in the Sprague-Dawley rat, was greater than 22.7 mg/L.
Executive summary:

The acute inhalation toxicity of the test material was investigated in a study which was conducted in accordance with the standardised guideline EU Method B.2, under GLP conditions.

During the study, a group of ten Sprague Dawley rats (five males and five females) was exposed to a vapour atmosphere. The animals were exposed for four hours using a nose only exposure system, followed by a fourteen day observation period.

Only one death occurred in a group of ten rats exposed to a mean achieved atmosphere concentration of 22.7 mg/L for four hours.

Common abnormalities noted during the study included increased respiratory rate, hunched posture, pilo erection and wet fur. There were isolated instances of laboured respiration and red/brown staining to the eyes. Surviving animals recovered quickly to appear normal from Day 1 post exposure.

Normal bodyweight development was noted during the study.

No macroscopic abnormalities were detected amongst animals necropsied at terminal kill. The animal that died during the study showed abnormally red lungs.

It was therefore considered that the acute inhalation median lethal concentration (4 hr LC50) of the test material, in the Sprague-Dawley rat, was greater than 22.7 mg/L.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
A GLP study conducted in accordance with a standardised guideline is available together with peer reviewed handbook data. The quality of the database is high.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
not specified
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Reference:
Composition 0
Qualifier:
no guideline followed
Principles of method if other than guideline:
Publication data does not specify the method.

Reference to orignal publication: Moreno, O.M. (1977) Report to RIFM, 7 October
GLP compliance:
not specified
Test type:
other: Not specified
Test material information:
Composition 1
Species:
rabbit
Strain:
not specified
Sex:
not specified
Type of coverage:
not specified
Key result
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
not specified
Interpretation of results:
study cannot be used for classification
Conclusions:
According to information in secondary literature, the acute dermal LD50 of the substance to the rabbit is in excess of 5000 mg/kg.
Executive summary:

According to information in secondary literature, the acute dermal LD50 of the substance to the rabbit is in excess of 5000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute Oral

Sax's Handbook

According to the handbook data the acute oral LD50 to rats is 5000 mg/kg, the acute oral LD50 to mice is 3460 mg/kg and the lethal dose low to the rabbit is 2550 mg/kg.

Food and Chemical Toxicology

The acute oral LD50 of the substance to rabbits was reported to be 2.5 - 3.2 g/kg with production of ataxia, gasping respirations and hypothermia at lethal dose levels (Browning, 1965, and Fasset, 1963) and 2.02 g/kg by Munch, 1972.

Acute Inhalation

SafePharm Laboratories - EU Method B.4 (rat)

The acute inhalation toxicity of the test material was investigated in a study which was conducted in accordance with the standardised guideline EU Method B.2, under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

During the study, a group of ten Sprague Dawley rats (five males and five females) was exposed to a vapour atmosphere. The animals were exposed for four hours using a nose only exposure system, followed by a fourteen day observation period.

Only one death occurred in a group of ten rats exposed to a mean achieved atmosphere concentration of 22.7 mg/L for four hours.

Common abnormalities noted during the study included increased respiratory rate, hunched posture, pilo erection and wet fur. There were isolated instances of laboured respiration and red/brown staining to the eyes. Surviving animals recovered quickly to appear normal from Day 1 post exposure.

Normal bodyweight development was noted during the study.

No macroscopic abnormalities were detected amongst animals necropsied at terminal kill. The animal that died during the study showed abnormally red lungs.

It was therefore considered that the acute inhalation median lethal concentration (4 hr LC50) of the test material, in the Sprague-Dawley rat, was greater than 22.7 mg/L.

Supporting information is available from handbook data. This handbook contains peer reviewed data where the test methodology and identity of the substance have been evaluated, and a reliable and representative value for the endpoint has been selected. No information on GLP status or test guideline followed is available. However, the data are awarded a reliability score of 2 in accordance with the criteria set forth by Klimisch et al. (1997) and support the findings from the rat study.

Sax's Handbook

According to handbook data the acute inhalation LC50 of the substance to mice is 27 g/m³.

Acute Dermal Toxicity

Food and Chemical Toxicology

According to information in secondary literature, the acute dermal LD50 of the substance to the rabbit is in excess of 5000 mg/kg.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No. 1272/2008, the substance does not require classification with respect to acute toxicity via the oral, dermal or inhalation routes.